A High Pretreatment Serum Basic Fibroblast Growth Factor Concentration Is an Independent Predictor of Poor Prognosis in Non-Hodgkin’s Lymphoma

Abstract

Basic fibroblast growth factor (bFGF) is a secreted multifunctional cytokine and a potent stimulator of angiogenesis in vivo. Elevated bFGF concentrations have been detected in the serum and urine of cancer patients. We measured bFGF by enzyme-linked immunosorbent assay from sera taken from 160 non-Hodgkin’s lymphoma (NHL) patients before treatment and stored at −20°C. The patients had been observed for at least 5 years or until death. Serum bFGF concentrations (S-bFGF) ranged from undetectable to 34.7 pg/mL (median, 3.3 pg/mL). S-bFGF was detectable with a similar frequency in all subtypes of NHL. A high pretreatment S-bFGF was associated with poor overall survival. The 5-year survival rate of the patients within the highest quartile of S-bFGF concentrations (S-bFGF = 5.5 pg/mL) was only 39%, in contrast to a 60% survival rate of the patients with lower S-bFGF (P = .019). A high S-bFGF (within the highest quartile) was associated with poor outcome also in large-cell diffuse and immunoblastic lymphomas (5-year survival rates of 28% v56%, respectively; P = .027), which was the largest histologic subgroup (n = 66) within the series. In multivariate analyses, S-bFGF was an independent prognostic factor, both when the highest quartile was used as a cut-off value (P = .0079) and when S-bFGF and the other parameters were entered into the model as continuous variables (P = .024). In the multivariate analyses, S-bFGF had a noticeably stronger prognostic value than serum lactate dehydrogenase and the number of extranodal tumor sites, both of which are currently included as components in the International Prognostic Index.